{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T01:33:31Z","timestamp":1773797611282,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science (JSPS)","award":["P20412"],"award-info":[{"award-number":["P20412"]}]},{"name":"Japan Society for the Promotion of Science (JSPS)","award":["22K21011"],"award-info":[{"award-number":["22K21011"]}]},{"name":"Japan Society for the Promotion of Science (JSPS)","award":["23H03078"],"award-info":[{"award-number":["23H03078"]}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["P20412"],"award-info":[{"award-number":["P20412"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["22K21011"],"award-info":[{"award-number":["22K21011"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["23H03078"],"award-info":[{"award-number":["23H03078"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Synthetic oligodeoxynucleotides (ODNs) containing unmethylated cytosine\u2013phosphate\u2013guanine (CpG) motifs (CpG-ODNs) are ligand molecules for Toll-like receptor 9 (TLR9), which is expressed by odontoblasts in vitro and dental pulp cells. This study determined the effects of CpG-ODNs on pulpal immunomodulatory response and repair following injury. Briefly, the upper right first molars of three-week-old mice were extracted, immersed in Type A (D35) or B (K3) CpG-ODN solutions (0.1 or 0.8 mM) for 30 min, and then replanted. Pulpal healing and immunomodulatory activity were assessed by hematoxylin\u2013eosin and AZAN staining, as well as immunohistochemistry. One week following the operation, inflammatory reactions occurred in all of the experimental groups; however, re-revascularization and newly formed hard tissue deposition were observed in the pulp chamber of all groups at week 2. A positive trend in the expression of immune cell markers was observed toward the CpG-ODN groups at 0.1 mM. Our data suggest that synthetic CpG-ODN solutions at low concentrations may evoke a long-lasting macrophage\u2013TLR9-mediated pro-inflammatory, rather than anti-inflammatory, response in the dental pulp to modulate the repair process and hard tissue formation. Further studies are needed to determine the effects of current immunomodulatory agents in vitro and in vivo and develop treatment strategies for dental tissue regeneration.<\/jats:p>","DOI":"10.3390\/biom14080931","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T12:38:20Z","timestamp":1722515900000},"page":"931","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effects of Synthetic Toll-Like Receptor 9 Ligand Molecules on Pulpal Immunomodulatory Response and Repair after Injuries"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6449-4631","authenticated-orcid":false,"given":"Angela","family":"Quispe-Salcedo","sequence":"first","affiliation":[{"name":"Division of Anatomy and Cell Biology of the Hard Tissue, Niigata University Graduate School of Medical and Dental Science, Niigata 951-8514, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2136-8042","authenticated-orcid":false,"given":"Tomohiko","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Research Center for Macromolecules and Biomaterials, National Institute of Material Sciences (NIMS), Tsukuba 305-0047, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-9900","authenticated-orcid":false,"given":"Hayato","family":"Ohshima","sequence":"additional","affiliation":[{"name":"Division of Anatomy and Cell Biology of the Hard Tissue, Niigata University Graduate School of Medical and Dental Science, Niigata 951-8514, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1146\/annurev.immunol.20.100301.064842","article-title":"CpG motifs in bacterial DNA and their immune effects","volume":"20","author":"Krieg","year":"2002","journal-title":"Annu. 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